2013
DOI: 10.1038/protex.2013.019
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Direct differentiation of hepatic stem-like WB cells into insulin-producing cells using small molecules

Abstract: Recent evidence suggests that experimental induction of hepatocytes into pancreatic cells provides new cell transplantation therapy prospects for type 1 diabetes mellitus. Stepwise differentiation from rat liver epithelial stem-like WB-F344 cells (WB cells) into functional insulin-secreting cells will identify key steps in b-cell development and may yet prove useful for transplantation therapy for diabetic patients. An essential step in this protocol was the generation of pancreatic precursor cell that express… Show more

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Cited by 13 publications
(15 citation statements)
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“…In addition, Li et al created endodermal progenitor cells by transiently overexpressing OCT4 , SOX2, KLF4 , and CMYC (OKSM) in mouse embryonic fibroblasts (MEFs) combined with small molecule epigenetic modifiers, which could subsequently be converted to β -cells [ 18 ]. Several recent studies have treated human or swine fibroblasts [ 19 21 ], mesenchymal stem cells [ 22 ], or rat liver stem cells [ 23 ], with epigenetic modifying molecules (DNA methyltransferase inhibitor and/or histone deacetylase inhibitor) in CRM followed by culture under β -cell specifying conditions. This combined treatment resulted in the generation of endocrine pancreatic β -cells that reversed hyperglycemia in immunodeficient mice.…”
Section: Introductionmentioning
confidence: 99%
“…In addition, Li et al created endodermal progenitor cells by transiently overexpressing OCT4 , SOX2, KLF4 , and CMYC (OKSM) in mouse embryonic fibroblasts (MEFs) combined with small molecule epigenetic modifiers, which could subsequently be converted to β -cells [ 18 ]. Several recent studies have treated human or swine fibroblasts [ 19 21 ], mesenchymal stem cells [ 22 ], or rat liver stem cells [ 23 ], with epigenetic modifying molecules (DNA methyltransferase inhibitor and/or histone deacetylase inhibitor) in CRM followed by culture under β -cell specifying conditions. This combined treatment resulted in the generation of endocrine pancreatic β -cells that reversed hyperglycemia in immunodeficient mice.…”
Section: Introductionmentioning
confidence: 99%
“…In both situations, administration of the Pdx1 protein induced hepatic cells to upregulate expression of pancreatic endocrine lineage-specific genes, such as NeuroD and insulin. 34,49 We hypothesized that FP will similarly be able to promote transdifferentiation of the rat liver stem-like WB-F344 cell line [49][50][51] into pancreatic endocrine progenitors. Hence, we cultured WB-F344 cells with 0.108 mM FP and assessed the dynamics of FP internalization by immunofluorescent staining for PDX1 ( Figure 3A).…”
Section: Fp Treatment Of Naive T Cells Results In An Emergence Of Funmentioning
confidence: 99%
“…The induction of the differentiation of cells from the liver in the endocrine pancreas is an attractive strategy because the liver and pancreas have the same precursors at the embryonic endoderm stage 89 . Liu et al therefore reprogrammed rat liver epithelial stem-cell-like WB-F344 cells (WB cells) into small-molecule-mediated insulinsecreting cells (SmISCs) in three stages 90 . First, they treated WB cells with 5-aza-2′-deoxycytidine (an inhibitor of DNA methylase, 5-AZA) for 2 days, followed by trichostatin A (a regulator of chromatin remodeling, TSA) for 1 day.…”
Section: β Cellsmentioning
confidence: 99%